Team:UCL/Project

Circuit Overview

Our genetic circuit aims primarily to remove amyloid plaques in the brain, which are associated with Alzheimer’s disease, prevent neuroinflammation and support neurons.

Detection

Senile plaques increase the rate of production of reactive oxygen species that are damaging to brain cells. We developed an oxidative stress promoter, in order to initiate the production of other circuit parts.

Chemotaxis

Microglia readily migrate towards plaques in vivo, but to see if we could increase migration to plaques, we produced a chemoattractant to help them converge.

Degradation

We expressed and characterised a matrix metalloproteinase that is capable of degrading amyloid. By increasing its expression in de-activated microglia, we hope to reduce amyloid burden in Alzheimer’s disease.

Selectable Marker

We used resistance to zeocin, a cell killing glycoprotein, to act as a selectable marker for transformation/transfection in our chassis; E.coli, HeLa and microglia.

Chassis

We conducted our experiments in three chassis, creating recombinant plasmids in E.coli before expressing them in HeLa and finally primary and immortalised human microglia lines.

Parts

We submitted X parts to the registry, LIST GENE NAMES and improved X, LIST GENE NAMES. To be filled in later

Future Developments

Our circuit design is far from finished; given sufficient time in the lab, we would have included several other important components, including the de-activating agent VIP and the support factor BDNF.